The phenotypic spectrum of McCune–Albright syndrome: a report of four paediatric cases and a literature review

Abstract Objectives McCune–Albright syndrome (MAS) is a rare mosaic disorder caused by postzygotic activating variants in GNAS , resulting in constitutive activation of stimulatory G protein alpha subunit (Gsα) signalling. The phenotype classically includes fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies, but the clinical spectrum extends beyond this triad. We describe four paediatric cases and review the current literature, with emphasis on the diagnostic challenges of mosaicism, endocrine morbidity and evolving treatment. Case presentation The four cases comprise a boy with polyostotic fibrous dysplasia, hyperthyroidism and Sertoli-cell hyperplasia; a girl with early fractures, peripheral precocious puberty, suspected phosphate wasting and craniofacial fibrous dysplasia; an adolescent with segmental pigmentation, pain and MRI-confirmed fibrous dysplasia after negative blood and skin testing; and a girl with very early gonadotropin-independent precocious puberty, transient hepatobiliary abnormalities and positive GNAS testing from a café-au-lait macule but no MRI evidence of fibrous dysplasia. Conclusions MAS is a dynamic multisystem mosaic disorder in which manifestations may emerge at different ages and in no fixed order. Negative blood testing does not exclude the diagnosis. Longitudinal endocrine, skeletal, ophthalmological and multidisciplinary surveillance is essential, and treatment should be directed at both endocrine control and preservation of skeletal function.